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NM_000474.4(TWIST1):c.328C>T (p.Arg110Trp) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 2, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000797570.6

Allele description

NM_000474.4(TWIST1):c.328C>T (p.Arg110Trp)

Gene:
TWIST1:twist family bHLH transcription factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p21.1
Genomic location:
Preferred name:
NM_000474.4(TWIST1):c.328C>T (p.Arg110Trp)
HGVS:
  • NC_000007.14:g.19116994G>A
  • NG_008114.2:g.5679C>T
  • NM_000474.4:c.328C>TMANE SELECT
  • NP_000465.1:p.Arg110Trp
  • NC_000007.13:g.19156617G>A
  • NM_000474.3:c.328C>T
  • NR_149001.2:n.643C>T
Protein change:
R110W
Links:
dbSNP: rs1585617188
NCBI 1000 Genomes Browser:
rs1585617188
Molecular consequence:
  • NM_000474.4:c.328C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_149001.2:n.643C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
TWIST1-related craniosynostosis (CRS1)
Synonyms:
Craniosynostosis 1
Identifiers:
MONDO: MONDO:0007399; MedGen: C4551902; Orphanet: 63440; OMIM: 123100
Name:
Saethre-Chotzen syndrome (SCS)
Synonyms:
ACS III; Acrocephalo-syndactyly, type 3; Chotzen syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007042; MedGen: C0175699; Orphanet: 794; OMIM: 101400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000937133Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 2, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000937133.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg110 amino acid residue in TWIST1. Other variant(s) that disrupt this residue have been observed in individuals with TWIST1-related conditions (Invitae), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TWIST1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 110 of the TWIST1 protein (p.Arg110Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024